ABSTRACT
TRPC proteins are ubiquitously expressed in almost all mammalian tissues with varying expression levels and functional signicance (Abramowitz and Birnbaumer, 2009). TRPC2 is a
Contents 27.1 Introduction 411 27.2 Biophysics and pharmacology of TRPC channels 411
27.2.1 Basic structural features 411 27.2.2 Activation mechanisms 412
27.2.2.1 Phospholipase C signaling 412 27.2.2.2 Gi/o protein signaling 413 27.2.2.3 Other mechanisms 414
27.2.3 TRPC channel modulation 414 27.2.3.1 Phosphorylation 414 27.2.3.2 Eects of cations 414 27.2.3.3 Regulated tracking and translocation to plasma membrane 414
27.2.4 Biophysical properties 414 27.2.4.1 Ionic selectivity and eects on membrane excitability 414 27.2.4.2 Voltage dependence 416
27.2.5 Pharmacology 416 27.3 Physiological functions of TRPC channels 417
27.3.1 TRPC channels in neuronal development and survival 417 27.3.2 TRPC channels in synaptic transmission 417
27.3.2.1 Cerebellum 417 27.3.2.2 Hippocampus 418 27.3.2.3 Hypothalamus 418 27.3.2.4 Other brain areas 419
27.3.3 TRPC channel functions in other body systems 420 27.4 Concluding remarks 420 Acknowledgment 421 References 421
pseudogene in humans, but in rodents it plays a central role in pheromone sensing (Freichel et al., 2004). All TRP channels are thought to be tetramers composed of either identical or related subunits. Each TRPC subunit is composed of six transmembrane segments (S1-S6) with both the amino (N)- and carboxyl (C)-termini located at the cytoplasmic side. A pore loop is found between S5 and S6, similar to the architecture of voltage-gated K+ (Kv) channels, and determines ion selectivity. Based on sequence homology, TRPCs are subdivided into four groups, TRPC1, TRPC2, TRPC3/C6/C7, and TRPC4/C5. e latter two groups share about 75% and 65% amino acid identities among members within the groups, respectively. All TRPC members contain an absolutely conserved amino acid motif, EWKFAR, termed TRP domain, at their C-termini (Figure 27.1). ey also have ankyrin (ANK)-like repeats at their N-termini and another conserved motif, namely, calmodulin (CaM) and IP3 receptor-binding (CIRB) site at their C-termini (Tang et al., 2001; Zhang et al., 2001; Clapham, 2003). In addition, individual TRPC isoforms also interact with a diverse range of other proteins, for example, Homer, junctate, NHERF, and stromal interaction molecule 1 (STIM1), many of which have been covered extensively in recent reviews (Kiselyov et al., 2005; Eder et al., 2007b; Ong and Ambudkar, 2011).
